Effect of Corticosteroid Treatment on Salicylate Ototoxicity

Our previous studies showed that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and elevated levels of leukotrienes (LTs) in the perilymph. The purpose of this study was to determine whether or not pretreatment with corticosteroid, which suppresses both PGs and LTs in arachidonic acid metabolism, prevents salicylate ototoxicity. Salicylate ototoxicity was induced in chinchillas with or without treatment with dexamethasone. Hearing thresholds were measured by auditory brain stem response, and perilymph samples were assayed by high-performance liquid chromatography. Dexamethasone pretreatment, given by either systemic or local round window membrane application, partially prevented salicylate-induced hearing loss. Prevention of salicylate ototoxicity by dexamethasone seems to be correlated with increased PG levels and decreased LT levels in the perilymph. This is another piece of evidence that salicylate ototoxicity may be mediated by abnormal arachidonic acid metabolism in the inner ear.

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Aspirin Preferentially Inhibits Arachidonic Acid Metabolism In Collagen Vs. Thrombin-Stimulated Platelets

10.1055/s-0038-1652092 ◽

1981 ◽

Author(s):

D Deykin ◽

R Vaillancourt

Keyword(s):

High Performance Liquid Chromatography ◽

Arachidonic Acid ◽

Liquid Chromatography ◽

High Performance ◽

Acid Metabolism ◽

Gel Filtration ◽

Human Platelets ◽

Arachidonic Acid Metabolism ◽

Selective Effect ◽

Oxygenase Activity

The purpose of this study was to compare the effect of aspirin on the release of metabolites of arachidonic acid from thrombin and collagen stimulated platelets. Human platelets were incubated with tritium-labeled arachidonic acid and then isolated by gel filtration. The labeled platelets were stimulated with varied doses of either thrombin or collagen for 15 minutes. The platelets were then pelleted and the released metabolites of arachidonic acid were separated by high-performance liquid chromatography. In experiments with aspirin, the aspirin was added 5 minutes before either thrombin or collagen. The total release of radioactivity was comparable at 15 μg/ml of collagen and 1.0 units/ml of thrombin (approximately 10% of the total) and at 100 μg/ml of collagen and 5 units/ml of thrombin (approximately 30%). Aspirin (25 μg/ml) preferentially inhibited collagen-stimulated release of radioactivity (62% inhibition of release with 15 μg/ml of collagen vs. 25% inhibition of release with 1.0 units/ml of thrombin; 54% inhibition of release with 100 μg/ml of collagen vs. 8% inhibition of release with 5.0 units/ml of thrombin). At all concentrations of collagen or thrombin, cyclo-oxygenase activity was markedly reduced by aspirin. The selective effect of aspirin on collagen reflects primarily preferential suppression of HETE formation. We conclude that aspirin inhibits the formation of both lipoxygenase and cyclooxygenase-derived products in collagen-stimulated platelets.

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Spontaneous Remission in Experimental Autoimmune Labyrinthitis

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949210101208 ◽

1992 ◽

Vol 101 (12) ◽

pp. 1007-1014 ◽

Cited By ~ 18

Author(s):

Shigeharu Yamanobe ◽

Jeffrey P. Harris

Keyword(s):

Inner Ear ◽

Time Course ◽

Round Window ◽

Spontaneous Remission ◽

Intradermal Injection ◽

Round Window Membrane ◽

Cellular Infiltration ◽

Auditory Brain Stem Response ◽

Hearing Thresholds ◽

Experimental Autoimmune

We investigated the time course of hearing impairment and cellular infiltration into the inner ear after systemic sensitization of guinea Pigs with a single intradermal injection of bovine inner ear antigen (IEAg) in complete Freund's adjuvant (CFA). Lymphocytes and polymorphonucleocytes appeared mainly in the scala tympani on days 7 to 14, and in addition there was thickening and cellular infiltration of the round window membrane at day 14. These cellular infiltrations resolved after day 28. The auditory brain stem response thresholds from IEAg-sensitized animals were significantly elevated after day 7. Some sensitized animals (n = 5) had spontaneous remissions after day 28; however, the hearing thresholds did not completely recover. These results demonstrate that experimental autoimmune labyrinthitis can be induced by a single inoculation of IEAg-CFA and that remission, as evidenced by clearing of the cochlear cellular infiltration and improved hearing thresholds, can occur spontaneously.

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Analysis by high performance liquid chromatography of cyclooxygenase products of arachidonic acid metabolism in plasma of rabbits bearing the VX2 carcinoma

Prostaglandins and Medicine ◽

10.1016/0161-4630(80)90017-8 ◽

1980 ◽

Vol 4 (4) ◽

pp. 227-237 ◽

Cited By ~ 12

Author(s):

Iftekhar Alam ◽

Edward F. Voelkel ◽

Armen H. Tashjian ◽

Lawrence Levine

Keyword(s):

High Performance Liquid Chromatography ◽

Arachidonic Acid ◽

Liquid Chromatography ◽

High Performance ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Vx2 Carcinoma

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Auditory brain stem response changes after application of endotoxin to the round window membrane in experimental otitis media☆, ☆☆, ★, ★★

Otolaryngology ◽

10.1016/s0194-5998(95)70211-3 ◽

1995 ◽

Vol 112 (4) ◽

pp. 557-565 ◽

Cited By ~ 1

Author(s):

I SCHWARTZ ◽

C KIM ◽

H KIM

Keyword(s):

Brain Stem ◽

Otitis Media ◽

Round Window ◽

Round Window Membrane ◽

Auditory Brain Stem Response ◽

Auditory Brain Stem ◽

Brain Stem Response

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Auditory Brain Stem Response Changes after Application of Endotoxin to the Round Window Membrane in Experimental Otitis Media

Otolaryngology ◽

10.1177/019459989511200409 ◽

1995 ◽

Vol 112 (4) ◽

pp. 557-565 ◽

Cited By ~ 11

Author(s):

Chong-Sun Kim ◽

Hyung-Jong Kim

Keyword(s):

Brain Stem ◽

Otitis Media ◽

Round Window ◽

Response Threshold ◽

Round Window Membrane ◽

Auditory Brain Stem Response ◽

Tube Obstruction ◽

Auditory Brain Stem ◽

Intratympanic Injection ◽

Brain Stem Response

The effects of endotoxin (purified Escherichia coli lipopolysaccharide 0111: B4) on cochlear function in normal and otitis media animals were evaluated. Two types of experimental otitis media models were developed in guinea pigs: eustachian tube obstruction and intratympanic injection of endotoxin. In normal animals, three different concentrations (0.01, 0.1, or 1.0 mg/ml) of endotoxin were applied onto the round window membrane, and auditory brain stem responses were recorded at 1, 3, 6, and 12 hours and 1, 2, 3, and 14 days after the application of endotoxin. Concentrations of 0.01 and 0.1 mg/ml of endotoxin did not affect the auditory brain stem response thresholds, whereas a concentration of 1.0 mg/ml resulted in elevation of the auditory brain stem response thresholds. Alteration of the auditory brain stem response threshold began at 3 hours, reached a peak at 24 or 48 hours, and returned to a normal level 2 weeks after the application of endotoxin. However, when the same concentration (1.0 mg/ml) of endotoxin was applied to the round window membranes of animals that underwent eustachian tube obstruction or intratympanic injection of endotoxin, the endotoxin did not cause any alteration of the auditory brain stem response threshold compared with normal animals.

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